The idic(X)(q13) in myeloid malignancies: breakpoint clustering in segmental duplications and association with TET2 mutations.

Paulsson, KajsaLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine (author)

Myelodysplastic syndromes and acute myeloid leukemia with an isodicentric X chromosome [idic(X)(q13)] occur in elderly women and frequently display ringed sideroblasts. Because of the rarity of idic(X)(q13), little is known about its formation, whether a fusion gene is generated, and patterns of additional aberrations. We here present a SNP array study of 14 idic(X)-positive myeloid malignancies, collected through an international collaborative effort. The breakpoints clustered in two regions of segmental duplications and were not in a gene, making dosage effects from the concurrent gain of Xpter-q13 and loss of Xq13-qter, rather than a fusion gene, the most likely pathogenetic outcome. Methylation analysis revealed involvement of the inactive X chromosomes in five cases and of the active in two. The ABCB7 gene, mutated in X-linked sideroblastic anemia and spinocerebellar ataxia, is in the deleted region, suggesting that loss of this gene underlies the frequent presence of ringed sideroblasts. Additional genetic abnormalities were present in 12/14 (86%), including partial uniparental disomies for 9p (1 case) and 4q (2 cases) associated with homozygous mutations of JAK2 and TET2, respectively. In total, TET2 mutations were seen in 4/11 (36%) analyzed cases, thus constituting a common secondary event in idic(X)-positive malignancies.

Haferlach, Claudia (author)
Fonatsch, Christa (author)
Hagemeijer, Anne (author)
Klarskov Andersen, Mette (author)
Slovak, Marilyn L (author)
Johansson, BertilLund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)kgen-bjo (author)
Avdelningen för klinisk genetikInstitutionen för laboratoriemedicin (creator_code:org_t)

In:Human Molecular Genetics: Oxford University Press (OUP)19, s. 1507-15140964-69061460-2083

By the author/editor: Paulsson, Kajsa; Haferlach, Claud ...; Fonatsch, Christ ...; Hagemeijer, Anne; Klarskov Anderse ...; Slovak, Marilyn ...; show more...; Johansson, Berti ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.